Alzheimer’s disease remains one of the most feared illnesses of our time, impacting more than six million people in the United States alone.
With no cure available, scientists are constantly exploring new ways to understand and treat this debilitating condition.
A new study led by Dr. Mike Greicius at Stanford Medicine offers compelling evidence that a common gene variant, APOE4, plays a direct and harmful role in the development of Alzheimer’s.
Traditionally, researchers have focused on amyloid plaque—a buildup of protein clusters in the brain—as a hallmark of Alzheimer’s.
While some treatments have targeted these plaques in hopes of reversing or halting the disease, many of these drugs have failed to show meaningful clinical improvements. This has led scientists to look beyond plaques and consider other factors, including genetic ones.
One of the most important genetic factors in Alzheimer’s is the APOE gene, which comes in several versions: APOE2, APOE3, and APOE4. Most people carry two copies of APOE3.
However, around 25% of people of European ancestry carry at least one copy of APOE4, and this variant is found in up to 60% of Alzheimer’s patients of European descent. Carrying one copy of APOE4 can double or triple your risk, while having two copies increases the risk up to tenfold.
The new study, published in Neuron in 2024, found two elderly individuals who carried a broken version of APOE4 that did not produce its typical protein.
Surprisingly, these individuals showed no signs of cognitive decline, even into their late 70s and 90s. One had no plaque buildup in the brain upon autopsy, and the other had normal cerebrospinal fluid levels of Alzheimer’s biomarkers at age 76.
These findings suggest that it is not the absence of APOE4 activity that is harmful, but its presence. ApoE4 may be actively toxic in the brain, setting off harmful processes long before symptoms appear. If this is true, then treatments should aim to reduce or eliminate ApoE4 activity, rather than boost it.
Interestingly, APOE4’s effects vary across ethnic groups. For example, people of African descent are more likely to carry APOE4, but they have a lower risk of developing Alzheimer’s than Europeans or Japanese with the same variant. This suggests that environmental or genetic modifiers may influence APOE4’s impact.
The study has also shed light on the complex nature of this gene’s function. ApoE is known to help transport fats throughout the body and may be involved in immune responses. Despite this, a drug that reduces but does not eliminate ApoE function could still be safe and effective, especially for people carrying two copies of APOE4.
Dr. Greicius and his team believe their findings finally give researchers a clear direction. ApoE4 is not a passive player—it’s actively contributing to the disease. Targeting and reducing ApoE4’s toxic effects could be the breakthrough Alzheimer’s research needs.
If you care about Alzheimer’s, please read studies about the likely cause of Alzheimer’s disease , and new non-drug treatment that could help prevent Alzheimer’s.
For more health information, please see recent studies about diet that may help prevent Alzheimer’s, and results showing some dementia cases could be prevented by changing these 12 things.
The study is published in Neuron.
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